This research with adolescents will investigate the relationship between genetic markers, personality characteristics and self-control, and health-related behaviors, with a focus on cigarette smoking. The research tests an epigenetic theoretical model, hypothesizing that genetic characteristics are related to substance use through dysregulation of self-control systems. We predict that selected genetic markers will be related to regular smoking in adolescence, and will manifest at the personality level as novelty seeking, hostility, and depression; at the physiological level as stress reactivity and deficits in cognitive executive functions; and at the level of generalized self- control as impatience, distractibility, and impulsivity. These characteristics are predicted to mediate at least part of the effect of genetic characteristics on cigarette smoking. In a two-stage design, a population of 1,800 school students (M age 14.5 years) will complete a self-report questionnaire in classrooms. The questionnaire will include measures of smoking frequency and perceived reinforcing effects; measures for personality and self-control; and measures of physical exercise frequency, dietary intake, and body mass index. Data from the survey will be used to draw samples of 120 regular smokers and 120 sex/race matched controls. These individuals will be examined in a clinical research center, with blood draw, neuropsychological assessment of executive functions, and a procedure for indexing physiological reactivity to stressors. Blood samples will be genotyped for dopamine receptors DRD2 and DRD4, COMT, and serotonin transporter. Association analyses will test for differential prevalence of specified alleles in smokers and nonsmokers; structural modeling analyses will test for relationships of genetic markers to personality and self-control variables. Exploratory hypotheses about the relation of study variables to obesity will also be examined.